Steven Deitelzweig - Academia.edu (original) (raw)

Papers by Steven Deitelzweig

Thrombosis Journal, Aug 21, 2015

Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin thera... more Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for reducing the risk of stroke in AF. However, warfarin has limitations that have motivated development of several novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that the NOACs offer efficacy and safety that are equivalent to, or better than, those of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This review examines stroke risk reduction in patients with AF from the perspective of the clinician balancing the risks and benefits of treatment options, evaluates the most recent guidelines, and discusses 2 hypothetical patient cases to better illustrate how clinicians may apply available data in the clinical setting. We reviewed guidelines for the reduction of stroke risk in AF and data from clinical trials on the NOACs. Choosing antithrombotic treatment involves assessing the benefits of therapy versus its risks. Risk indexes, including CHADS 2 , CHA 2 DS 2-VASc, and HAS-BLED can help determine how to treat patients with AF. Current guidelines suggest using these risk indexes to customize treatment to individual patients. Many current treatment guidelines also incorporate recommendations for the use of NOACs as an alternative to warfarin. As additional data emerge and guidelines are updated, these recommendations will likely evolve. In the interim, clinicians may consider published guidelines and clinical trial results on NOACs. Real-world experience will provide clinicians with additional insight into their treatment decisions.

Journal of the American College of Cardiology, Mar 1, 2023

JAMA network open, Aug 31, 2022

IMPORTANCE The CHA 2 DS 2-VASc score (calculated as congestive heart failure, hypertension, age 7... more IMPORTANCE The CHA 2 DS 2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. OBJECTIVE To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA 2 DS 2-VASc risk score range, thromboembolic event history, and age group. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. EXPOSURE Initiation of oral anticoagulants. MAIN OUTCOMES AND MEASURES We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA 2 DS 2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. RESULTS We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA 2 DS 2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 (continued) Key Points Question What are the relative safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving anticoagulants by CHA 2 DS 2-VASc risk score range, thromboembolic event history, and age group? Findings In this cohort study including data from more than 1 million patients, the observed incidence of stroke, systemic embolism, and major bleeding events generally conformed to an expected increasing incidence by risk score. Meaning These results suggest that the assessment of individual baseline risk profiles can better inform clinical decision-making, research, and policy for this patient population.

Blood, Nov 16, 2012

Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonv... more Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Journal of the American College of Cardiology, Mar 1, 2019

Background: Obesity has an important impact on general health outcomes and is prevalent in nonval... more Background: Obesity has an important impact on general health outcomes and is prevalent in nonvalvular atrial fibrillation (NVAF) patients. This study evaluated stroke/systemic embolism (SE) and major bleeding (MB) among obese NVAF patients using non-vitamin K antagonist oral anticoagulants (NOACs) in the ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study population. Methods: In this retrospective observational study, obese (identified using diagnosis codes) NVAF patients who initiated apixaban, dabigatran, or rivaroxaban treatment from 01JAN2013-30SEP2015 were selected from a pooled sample of Medicare and four US commercial claims data populations, covering >180 million beneficiaries annually. Propensity score matching (PSM) was used to balance baseline characteristics between patients prescribed NOACs. Cox models were used to evaluate the relative risk of stroke/SE and MB. Results: Matched pairs had 6-7 months of follow-up. Apixaban was associated with lower rates of stroke/SE and MB vs rivaroxaban and similar rates of stroke/SE and MB vs dabigatran. Dabigatran use showed lower rates of MB and similar rates of stroke/SE vs rivaroxaban (Figure). Conclusion: Among obese NVAF patients, apixaban and dabigatran were associated with lower rates of MB vs rivaroxaban; apixaban was associated with lower rates of stroke/SE, and dabigatran with similar stroke/SE rates vs rivaroxaban.

European Heart Journal, 2015

Circulation-cardiovascular Quality and Outcomes, Apr 1, 2012

Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) pat... more Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) patients is common. Hypothesis We hypothesized that in a managed care population, warfarin discontinuation is associated with increased stroke risk. Methods Patients who initiated warfarin therapy between Jan 2005 and Jun 2009 and had a healthcare claim related to AF within 30 days prior to the first warfarin claim, but no evidence of valvular disease, were included. Warfarin discontinuation was defined as a supply gap of >60 days without evidence of International Normalized Ratio (INR) measurements. Follow-up was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis for stroke or transient ischemic attack (TIA). Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the prior warfarin treatment period. Results The mean (SD) age of the study sample (N=16,253) was 67±12 years; 64.8% was male. Mean CHADS2 score was 1.84±1.30; mean HAS-BLED score was 2.00±1.18. Half (51.4%) of patients discontinued warfarin therapy at least once and the overall sample had a mean of 1.87 warfarin treatment periods during a mean of 668 days follow-up. Approximately 1186 patients (7%) had a stroke or TIA at any site of service during follow-up. Risk of stroke significantly increased during warfarin discontinuation periods compared with therapy periods (HR 1.60; 95%CI 1.35-1.90; P

Blood, Nov 16, 2012

Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonv... more Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF), and different anatomical sites may carry greater risk for bleeding. Objective: To describe the incidence of critical anatomical site bleeding events among patients with NVAF in the pre-NOAC (novel oral anticoagulation) era. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were considered major if they were associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Anatomical bleeding sites were identified based on diagnosis codes. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Over 105,419 patient-years, the critical site with the highest rate of major bleeding events was the gastrointestinal tract, followed by intracranial bleeding (TABLE). Conclusions: Gastrointestinal, intracranial, and pericardial bleedings were the most frequently observed major bleedings in the pre-NOAC era. Patients with NVAF have a high rate of major gastrointestinal bleedings. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Circulation-cardiovascular Quality and Outcomes, Apr 1, 2012

Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) require... more Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) requires careful assessment of both the risk of stroke and bleeding. Hypothesis We hypothesized that in a real-world managed care population of patients with NVAF, bleeding incidence increases with CHADS2 stroke risk. Methods Administrative claims data were used for this retrospective study. Adults with healthcare claims related to AF (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Patients were categorized based on CHADS2 scores of 0, 1, 2, or ≥3, with higher scores indicating more risk factors. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Results The mean (SD) age of the study sample (N=48,260) was 67±13 years and 62% of the patients were male. Mean follow-up duration was 802±540 days (median 673 days). Mean (SD) baseline CHADS2 score was 1.48±1.15. Event rates for each bleeding category increased with increasing CHADS2 scores (Table). Conclusions Patients with NVAF in a real-world managed care setting who had high stroke risk also had a high rate of bleeding events, including major events. Patients at high risk for stroke might require more careful selection of anticoagulation therapy to avoid bleeding events.

Value in Health, May 1, 2015

matched and analyzed to see if there any trend and relation between the number of drugs added in ... more matched and analyzed to see if there any trend and relation between the number of drugs added in the NHF and the percentage of deaths listed for each disease. Results: The NHF has drugs for every disease evaluated. In the period analyzed, the number of drugs for DM has increased from 18 to 24. In the case of IHD, the number has also grown from 20 to 32. For CD there has been also an addition from 10 to 13. The drugs for ALD is the same in each year (only one drug). At last, for COPD the number has change from 35 to 36 drugs. Comparing with the number of deaths, the IHD is the disease with the biggest increased of deaths (22%), then the DM with 12%, COPD 11%, ALD 4%, and CD 3%. ConClusions: Although there have been added new drugs prescribed for the diseases that caused the deaths of most population in the NHF, this quantity is not comparable with the growing of deaths observed in each disease.

Journal of the American College of Cardiology, Mar 1, 2012

Background: The AVERROES trial showed that apixaban reduced the risk of stroke or systemic emboli... more Background: The AVERROES trial showed that apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding when used among atrial fibrillation (AF) patients unable or unwilling to take warfarin. This study evaluates the medical costs avoided with the use of apixaban vs. aspirin, based on the AVERROES trial. Methods: A cost comparison analysis was conducted from the US perspective to compare total medical costs associated with apixaban vs. aspirin use for AF. The rates of primary and secondary efficacy and safety endpoints were obtained from the AVERROES trial. Annual incremental costs associated with each clinical event were obtained from published literature and inflation adjusted to 2010 costs. Total medical costs were compared for apixaban vs. aspirin. Sensitivity analyses evaluated the variation in total medical cost avoidance with clinical endpoint rates and costs ranging within the confidence intervals (CI) and by +/-20%, respectively. Results: Using AVERROES trial data, estimated efficacy and safety endpoint rates per patient year for apixaban were 1.43% [CI: 1.02-2.02] for ischemic or uncertain type of stroke (IS), 0.20% [CI: 0.07-0.56] for hemorrhagic stroke, 0.77% [CI: 0.45-1.33] for myocardial infarction (MI), and 1.16% [CI: 0.82-1.54] for major bleeding excluding hemorrhagic stroke (MB).

Expert Review of Pharmacoeconomics & Outcomes Research, Jun 19, 2019

Objectives: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Servi... more Objectives: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Service (NHS). Betrixaban is approved in the US for VTE prophylaxis with a recommended 35-42 days of treatment. This analysis modeled the budget impact of introducing betrixaban for extended-duration VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the UK, where it is not yet licensed. Methods: The 5-year budget impact of introducing betrixaban into current prophylaxis (low molecular weight heparin and fondaparinux) was estimated for the UK NHS. The Phase 3 APEX study provided primary event (VTE, myocardial infarction, ischemic stroke, and death; all-cause or VTE-related) and treatment complications data. Literature informed risk of recurrent events and long-term complications, population, market share, and costs for treatment and management of events. Network meta-analyses informed symptomatic DVT, pulmonary embolism and VTE-related death rates in fondaparinux patients. Deterministic sensitivity analyses explored uncertainty. Results: Introducing betrixaban accrued savings of £1,290,000-£23,000,000 in years 1-5. Savings were from reduced primary VTE events, which reduced recurrent events and future complications. All sensitivity analyses showed savings. Conclusion: Introducing extended-duration VTE prophylaxis with betrixaban in the UK would accrue substantial savings annually over the next 5 years compared to current prophylaxis. Clinical trial registration: www.clinicaltrials.gov identifier is NCT01583218.

Hospital practice, Jan 2, 2015

Abstract As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective a... more Abstract As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective as warfarin, often with superior safety for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. Currently, dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban, direct factor Xa inhibitors, has been approved in multiple countries for these indications. Edoxaban, which has received approval for the abovementioned indications in Japan, has demonstrated efficacy and safety comparable to or better than warfarin in Phase III clinical trials and is under further regulatory consideration. It is anticipated that the use of TSOACs will increase as practitioners and healthcare systems gain familiarity with these drugs and adopt their use into clinical practice. This review will provide a brief overview of the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic events in patients with AF and the Phase III clinical trials for the prevention of recurrent VTE, discuss current treatment guidelines, address how TSOACs may help meet national safety goals, and provide clinical decision-making guidance regarding the use of TSOACs for hospitalists.

Journal of the American College of Cardiology, Mar 1, 2019

The prevalence of obesity in nonvalvular atrial fibrillation (NVAF) patients is apparent in trial... more The prevalence of obesity in nonvalvular atrial fibrillation (NVAF) patients is apparent in trials and real-world studies; however, there is limited data on the effectiveness and safety of anticoagulation specific to this population. This study evaluated stroke/systemic embolism (SE) and major

Blood, Nov 19, 2010

Abstract 3824 Background: The Centers for Medicare and Medicaid Services (CMS) recently executed ... more Abstract 3824 Background: The Centers for Medicare and Medicaid Services (CMS) recently executed a policy which denies reimbursement for preventable hospital acquired conditions (HAC) (“never events”). Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing major surgical hip or knee procedures was a condition selected for implementation as part of this policy in fiscal year 2009 (beginning October 2008). The objective of this analysis was to estimate the financial impact of this policy change on US hospitals. Methods: Discharge-level hospital administrative records were extracted from the Thomson Reuters MarketScan® Hospital Drug Database for patients undergoing CMS-defined surgical hip and knee procedures (total hip/knee replacement, partial hip replacement, and hip resurfacing). Discharged patients meeting the following criteria were included: admission and discharge between October 2007 and September 2008, age ≥ 18 years, Medicare as primary payer, valid CMS hospital ID and no evidence of DVT/PE on admission. The frequency of CMS defined VTE was assessed and the economic impact of the CMS HAC policy was estimated. Revenue impact, the amount of revenue lost per hospital due to CMS policy implementation, was calculated per year and per VTE discharge using the old and new CMS reimbursement rules. The incremental cost impact, the additional cost to hospitals due to VTE among hip/knee surgery patients, was also determined. Results: A total of 107 hospitals were identified to have at least one eligible surgical hip and knee surgery discharge. The total number of such discharges was 26,144. On average, there were 244.34 CMS-defined hip/knee surgery discharges per hospital. The majority of discharged patients were from urban hospitals (83.37%) in the Southern US (73.07%), without teaching status (87.98%) and with a licensed bed size of 300–499 beds (31.90%). VTE occurred in an average (± standard deviation) of 4.25 ± 6.05 hip/knee surgery discharges per hospital; DVT and PE occurred in 2.44 ± 5.11 and 1.81 ± 1.89 discharges per hospital, respectively. The average length of hospital stay was 7.56 ± 2.88 days in hip/knee discharges with VTE, compared to 4.08 ± 0.59 days in discharges without VTE. Anticoagulation was ordered in 94.70% of discharged patients with DVT and in 89.06% of discharged patients with PE. Under the CMS HAC policy for VTE, the mean loss of revenue per hospital per year was estimated to be 8,453(958,453 (95% confidence interval [CI] 6,902 – 10,005). Per VTE, the average hospital revenue loss was 8,453(952,704 per hospital per year. The mean incremental cost for a hip/knee discharge with VTE, per hospital was 6,581;forDVTandPE,incrementalcostimpactswere6,581; for DVT and PE, incremental cost impacts were 6,581;forDVTandPE,incrementalcostimpactswere6,751 and 8,092,respectively.Theannualcostimpactperhospitalforhip/kneedischargeswithVTEwasestimatedat8,092, respectively. The annual cost impact per hospital for hip/knee discharges with VTE was estimated at 8,092,respectively.Theannualcostimpactperhospitalforhip/kneedischargeswithVTEwasestimatedat31,609 [95% CI 23,714 – 39,505]. Conclusions: The CMS policy on average caused a loss of hospital revenue (≂f$8,500 per year). Additionally, when a VTE event does occur in patients undergoing surgical hip and knee procedures, it is associated with high incremental hospital costs (≂f$32,000). These significant costs will no longer be reimbursed under the new CMS HAC policy. Subsequently, hospitals will be responsible for covering them. Therefore, now more than ever, reducing VTE rates through appropriate prophylaxis of at-risk patients is vital in order for hospitals to lessen the economic impact associated with treating VTE events. The drive to encourage hospitals to provide more efficient and effective healthcare is becoming particularly relevant now that models of health care reform, such as the “Accountable Care Organization”, are being piloted as part of the Senate's Healthcare Reform Bill. This study was funded by sanofi-aventis U.S., Inc. The authors received editorial/writing support in the preparation of this abstract provided by Katherine Roberts, PhD of Excerpta Medica, funded by sanofi-aventis U.S., Inc. Disclosures: Deitelzweig: sanofi-aventis: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Scios: Honoraria, Research Funding, Speakers Bureau; Pfizer: Speakers Bureau. Thompson:sanofi-aventis US Inc.: Employment. Lin:sanofi-aventis US Inc.: Employment, Research Funding. McMorrow:sanofi-aventis US Inc : Research Funding. Johnson:sanofi-aventis US Inc: Research Funding.

Journal of the American College of Cardiology, Mar 1, 2012

Background: This study compares the total medical costs with the use of the new oral anticoagulan... more Background: This study compares the total medical costs with the use of the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban vs. warfarin in the US, based on the results of the ARISTOTLE, RELY and ROCKET-AF trials. Methods: A cost comparison analysis was conducted from the US perspective. The rates of efficacy and safety endpoints for warfarin were estimated as the weighted averages from the ARISTOTLE, RELY and ROCKET-AF trials. The rates of clinical events for NOACs were calculated using the hazard ratios from the original trials. Annual incremental costs associated with clinical events from the US payer perspective were obtained from published literature and inflation adjusted to 2010 cost. Total medical cost avoidance was evaluated for each NOAC vs. warfarin. Results: Based on data from ARISTOTLE, RELY and ROCKET-AF, the per patient year event rates for warfarin treatment were estimated to be 1.24% for ischemic or uncertain type of stroke (IS), 0.75% for myocardial infarction (MI), and 2.83% for major bleeding excluding hemorrhagic stroke (MB). The estimated event rates were IS: 1.14% [

PharmacoEconomics, Dec 21, 2018

Background Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in... more Background Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in nonsurgical patients with acute medical illness. Betrixaban is the first anticoagulant approved in the United States (US) for VTE prophylaxis extending beyond hospitalization. Objective The aim was to establish whether betrixaban for VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the US is cost-effective compared with enoxaparin. Methods A cost-effectiveness analysis was conducted, estimating the cost per quality-adjusted life-year (QALY) gained with betrixaban (35-42 days) compared with enoxaparin (6-14 days) from a US payer perspective over a lifetime horizon. A decision tree (DT) estimated primary VTE events, thrombotic events, and treatment complications in the first 3 months based on data from the phase III Acute Medically Ill VTE Prevention with Extended Duration Betrixaban study. A Markov model estimated recurrent events and long-term complication risks from published literature. EuroQoL-5 Dimensions utility data and costs inflated to 2017 US dollars (US$) were from published literature. Results were discounted at 3.0% per annum. Deterministic and probabilistic sensitivity analyses explored uncertainty. Results Betrixaban dominated enoxaparin, with savings of US$784 and increased QALYs of 0.017 per patient. In addition, betrixaban dominated enoxaparin across all sensitivity analyses, but was most sensitive to utilities and DT probabilities. Furthermore, probabilistic sensitivity analysis found that betrixaban was more cost-effective than enoxaparin at all willingness-to-pay thresholds. Conclusion Betrixaban can be considered cost-effective for nonsurgical patients with acute medical illness at risk of VTE, requiring longer VTE prophylaxis from hospitalization through post-discharge.

Cleveland Clinic Journal of Medicine, Apr 1, 2008

Journal of the American College of Cardiology, Nov 1, 2022

Current Medical Research and Opinion, Dec 8, 2017

Abstract Objective: To conduct a systematic literature review (SLR) and network meta-analysis (NM... more Abstract Objective: To conduct a systematic literature review (SLR) and network meta-analysis (NMA) of real-world studies comparing major bleeding risk among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin. Methods: Systematic searches were conducted in MEDLINE and Embase for full-text articles published between January 1, 2003 and March 18, 2017. Eligible studies compared at least two of the following in a real-world setting: warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban. A Bayesian NMA was conducted to estimate hazard ratios (HRs) for major bleeding using a random-effects model. Results: Eleven studies were included in the NMA. Nine studies included DOACs vs Warfarin comparisons, and four studies included DOACs vs DOACs comparisons (two studies included both comparisons). Median follow-up duration ranged from 2.6–31.2 months. No evidence was identified for edoxaban. Apixaban was associated with a significantly lower risk of major bleeding compared to other oral anticoagulants (warfarin HR = 0.58; 95% credible interval [CrI] = 0.48–0.69; dabigatran = 0.73; 0.61–0.87; rivaroxaban = 0.55; 0.46–0.66). Dabigatran was associated with a significantly lower risk than warfarin (0.79; 0.71–0.88) and rivaroxaban (0.76; 0.67–0.85), and rivaroxaban was not statistically different from warfarin (1.05; 0.91–1.19). Sensitivity analyses with standard dose and sponsorship showed consistent results. Conclusion: DOACs were associated with lower or similar risk of major bleeding compared with warfarin in NVAF patients. Apixaban was associated with a significantly lower risk of major bleeding than other DOACs. Dabigatran was associated with a significantly lower risk of major bleeding compared to rivaroxaban and warfarin.

Thrombosis Journal, Aug 21, 2015

Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin thera... more Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for reducing the risk of stroke in AF. However, warfarin has limitations that have motivated development of several novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that the NOACs offer efficacy and safety that are equivalent to, or better than, those of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This review examines stroke risk reduction in patients with AF from the perspective of the clinician balancing the risks and benefits of treatment options, evaluates the most recent guidelines, and discusses 2 hypothetical patient cases to better illustrate how clinicians may apply available data in the clinical setting. We reviewed guidelines for the reduction of stroke risk in AF and data from clinical trials on the NOACs. Choosing antithrombotic treatment involves assessing the benefits of therapy versus its risks. Risk indexes, including CHADS 2 , CHA 2 DS 2-VASc, and HAS-BLED can help determine how to treat patients with AF. Current guidelines suggest using these risk indexes to customize treatment to individual patients. Many current treatment guidelines also incorporate recommendations for the use of NOACs as an alternative to warfarin. As additional data emerge and guidelines are updated, these recommendations will likely evolve. In the interim, clinicians may consider published guidelines and clinical trial results on NOACs. Real-world experience will provide clinicians with additional insight into their treatment decisions.

Journal of the American College of Cardiology, Mar 1, 2023

JAMA network open, Aug 31, 2022

IMPORTANCE The CHA 2 DS 2-VASc score (calculated as congestive heart failure, hypertension, age 7... more IMPORTANCE The CHA 2 DS 2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. OBJECTIVE To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA 2 DS 2-VASc risk score range, thromboembolic event history, and age group. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. EXPOSURE Initiation of oral anticoagulants. MAIN OUTCOMES AND MEASURES We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA 2 DS 2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. RESULTS We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA 2 DS 2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 (continued) Key Points Question What are the relative safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving anticoagulants by CHA 2 DS 2-VASc risk score range, thromboembolic event history, and age group? Findings In this cohort study including data from more than 1 million patients, the observed incidence of stroke, systemic embolism, and major bleeding events generally conformed to an expected increasing incidence by risk score. Meaning These results suggest that the assessment of individual baseline risk profiles can better inform clinical decision-making, research, and policy for this patient population.

Blood, Nov 16, 2012

Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonv... more Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Journal of the American College of Cardiology, Mar 1, 2019

Background: Obesity has an important impact on general health outcomes and is prevalent in nonval... more Background: Obesity has an important impact on general health outcomes and is prevalent in nonvalvular atrial fibrillation (NVAF) patients. This study evaluated stroke/systemic embolism (SE) and major bleeding (MB) among obese NVAF patients using non-vitamin K antagonist oral anticoagulants (NOACs) in the ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study population. Methods: In this retrospective observational study, obese (identified using diagnosis codes) NVAF patients who initiated apixaban, dabigatran, or rivaroxaban treatment from 01JAN2013-30SEP2015 were selected from a pooled sample of Medicare and four US commercial claims data populations, covering >180 million beneficiaries annually. Propensity score matching (PSM) was used to balance baseline characteristics between patients prescribed NOACs. Cox models were used to evaluate the relative risk of stroke/SE and MB. Results: Matched pairs had 6-7 months of follow-up. Apixaban was associated with lower rates of stroke/SE and MB vs rivaroxaban and similar rates of stroke/SE and MB vs dabigatran. Dabigatran use showed lower rates of MB and similar rates of stroke/SE vs rivaroxaban (Figure). Conclusion: Among obese NVAF patients, apixaban and dabigatran were associated with lower rates of MB vs rivaroxaban; apixaban was associated with lower rates of stroke/SE, and dabigatran with similar stroke/SE rates vs rivaroxaban.

European Heart Journal, 2015

Circulation-cardiovascular Quality and Outcomes, Apr 1, 2012

Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) pat... more Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) patients is common. Hypothesis We hypothesized that in a managed care population, warfarin discontinuation is associated with increased stroke risk. Methods Patients who initiated warfarin therapy between Jan 2005 and Jun 2009 and had a healthcare claim related to AF within 30 days prior to the first warfarin claim, but no evidence of valvular disease, were included. Warfarin discontinuation was defined as a supply gap of >60 days without evidence of International Normalized Ratio (INR) measurements. Follow-up was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis for stroke or transient ischemic attack (TIA). Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the prior warfarin treatment period. Results The mean (SD) age of the study sample (N=16,253) was 67±12 years; 64.8% was male. Mean CHADS2 score was 1.84±1.30; mean HAS-BLED score was 2.00±1.18. Half (51.4%) of patients discontinued warfarin therapy at least once and the overall sample had a mean of 1.87 warfarin treatment periods during a mean of 668 days follow-up. Approximately 1186 patients (7%) had a stroke or TIA at any site of service during follow-up. Risk of stroke significantly increased during warfarin discontinuation periods compared with therapy periods (HR 1.60; 95%CI 1.35-1.90; P

Blood, Nov 16, 2012

Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonv... more Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF), and different anatomical sites may carry greater risk for bleeding. Objective: To describe the incidence of critical anatomical site bleeding events among patients with NVAF in the pre-NOAC (novel oral anticoagulation) era. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were considered major if they were associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Anatomical bleeding sites were identified based on diagnosis codes. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Over 105,419 patient-years, the critical site with the highest rate of major bleeding events was the gastrointestinal tract, followed by intracranial bleeding (TABLE). Conclusions: Gastrointestinal, intracranial, and pericardial bleedings were the most frequently observed major bleedings in the pre-NOAC era. Patients with NVAF have a high rate of major gastrointestinal bleedings. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Circulation-cardiovascular Quality and Outcomes, Apr 1, 2012

Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) require... more Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) requires careful assessment of both the risk of stroke and bleeding. Hypothesis We hypothesized that in a real-world managed care population of patients with NVAF, bleeding incidence increases with CHADS2 stroke risk. Methods Administrative claims data were used for this retrospective study. Adults with healthcare claims related to AF (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Patients were categorized based on CHADS2 scores of 0, 1, 2, or ≥3, with higher scores indicating more risk factors. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Results The mean (SD) age of the study sample (N=48,260) was 67±13 years and 62% of the patients were male. Mean follow-up duration was 802±540 days (median 673 days). Mean (SD) baseline CHADS2 score was 1.48±1.15. Event rates for each bleeding category increased with increasing CHADS2 scores (Table). Conclusions Patients with NVAF in a real-world managed care setting who had high stroke risk also had a high rate of bleeding events, including major events. Patients at high risk for stroke might require more careful selection of anticoagulation therapy to avoid bleeding events.

Value in Health, May 1, 2015

matched and analyzed to see if there any trend and relation between the number of drugs added in ... more matched and analyzed to see if there any trend and relation between the number of drugs added in the NHF and the percentage of deaths listed for each disease. Results: The NHF has drugs for every disease evaluated. In the period analyzed, the number of drugs for DM has increased from 18 to 24. In the case of IHD, the number has also grown from 20 to 32. For CD there has been also an addition from 10 to 13. The drugs for ALD is the same in each year (only one drug). At last, for COPD the number has change from 35 to 36 drugs. Comparing with the number of deaths, the IHD is the disease with the biggest increased of deaths (22%), then the DM with 12%, COPD 11%, ALD 4%, and CD 3%. ConClusions: Although there have been added new drugs prescribed for the diseases that caused the deaths of most population in the NHF, this quantity is not comparable with the growing of deaths observed in each disease.

Journal of the American College of Cardiology, Mar 1, 2012

Background: The AVERROES trial showed that apixaban reduced the risk of stroke or systemic emboli... more Background: The AVERROES trial showed that apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding when used among atrial fibrillation (AF) patients unable or unwilling to take warfarin. This study evaluates the medical costs avoided with the use of apixaban vs. aspirin, based on the AVERROES trial. Methods: A cost comparison analysis was conducted from the US perspective to compare total medical costs associated with apixaban vs. aspirin use for AF. The rates of primary and secondary efficacy and safety endpoints were obtained from the AVERROES trial. Annual incremental costs associated with each clinical event were obtained from published literature and inflation adjusted to 2010 costs. Total medical costs were compared for apixaban vs. aspirin. Sensitivity analyses evaluated the variation in total medical cost avoidance with clinical endpoint rates and costs ranging within the confidence intervals (CI) and by +/-20%, respectively. Results: Using AVERROES trial data, estimated efficacy and safety endpoint rates per patient year for apixaban were 1.43% [CI: 1.02-2.02] for ischemic or uncertain type of stroke (IS), 0.20% [CI: 0.07-0.56] for hemorrhagic stroke, 0.77% [CI: 0.45-1.33] for myocardial infarction (MI), and 1.16% [CI: 0.82-1.54] for major bleeding excluding hemorrhagic stroke (MB).

Expert Review of Pharmacoeconomics & Outcomes Research, Jun 19, 2019

Objectives: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Servi... more Objectives: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Service (NHS). Betrixaban is approved in the US for VTE prophylaxis with a recommended 35-42 days of treatment. This analysis modeled the budget impact of introducing betrixaban for extended-duration VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the UK, where it is not yet licensed. Methods: The 5-year budget impact of introducing betrixaban into current prophylaxis (low molecular weight heparin and fondaparinux) was estimated for the UK NHS. The Phase 3 APEX study provided primary event (VTE, myocardial infarction, ischemic stroke, and death; all-cause or VTE-related) and treatment complications data. Literature informed risk of recurrent events and long-term complications, population, market share, and costs for treatment and management of events. Network meta-analyses informed symptomatic DVT, pulmonary embolism and VTE-related death rates in fondaparinux patients. Deterministic sensitivity analyses explored uncertainty. Results: Introducing betrixaban accrued savings of £1,290,000-£23,000,000 in years 1-5. Savings were from reduced primary VTE events, which reduced recurrent events and future complications. All sensitivity analyses showed savings. Conclusion: Introducing extended-duration VTE prophylaxis with betrixaban in the UK would accrue substantial savings annually over the next 5 years compared to current prophylaxis. Clinical trial registration: www.clinicaltrials.gov identifier is NCT01583218.

Hospital practice, Jan 2, 2015

Abstract As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective a... more Abstract As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective as warfarin, often with superior safety for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. Currently, dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban, direct factor Xa inhibitors, has been approved in multiple countries for these indications. Edoxaban, which has received approval for the abovementioned indications in Japan, has demonstrated efficacy and safety comparable to or better than warfarin in Phase III clinical trials and is under further regulatory consideration. It is anticipated that the use of TSOACs will increase as practitioners and healthcare systems gain familiarity with these drugs and adopt their use into clinical practice. This review will provide a brief overview of the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic events in patients with AF and the Phase III clinical trials for the prevention of recurrent VTE, discuss current treatment guidelines, address how TSOACs may help meet national safety goals, and provide clinical decision-making guidance regarding the use of TSOACs for hospitalists.

Journal of the American College of Cardiology, Mar 1, 2019

The prevalence of obesity in nonvalvular atrial fibrillation (NVAF) patients is apparent in trial... more The prevalence of obesity in nonvalvular atrial fibrillation (NVAF) patients is apparent in trials and real-world studies; however, there is limited data on the effectiveness and safety of anticoagulation specific to this population. This study evaluated stroke/systemic embolism (SE) and major

Blood, Nov 19, 2010

Abstract 3824 Background: The Centers for Medicare and Medicaid Services (CMS) recently executed ... more Abstract 3824 Background: The Centers for Medicare and Medicaid Services (CMS) recently executed a policy which denies reimbursement for preventable hospital acquired conditions (HAC) (“never events”). Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing major surgical hip or knee procedures was a condition selected for implementation as part of this policy in fiscal year 2009 (beginning October 2008). The objective of this analysis was to estimate the financial impact of this policy change on US hospitals. Methods: Discharge-level hospital administrative records were extracted from the Thomson Reuters MarketScan® Hospital Drug Database for patients undergoing CMS-defined surgical hip and knee procedures (total hip/knee replacement, partial hip replacement, and hip resurfacing). Discharged patients meeting the following criteria were included: admission and discharge between October 2007 and September 2008, age ≥ 18 years, Medicare as primary payer, valid CMS hospital ID and no evidence of DVT/PE on admission. The frequency of CMS defined VTE was assessed and the economic impact of the CMS HAC policy was estimated. Revenue impact, the amount of revenue lost per hospital due to CMS policy implementation, was calculated per year and per VTE discharge using the old and new CMS reimbursement rules. The incremental cost impact, the additional cost to hospitals due to VTE among hip/knee surgery patients, was also determined. Results: A total of 107 hospitals were identified to have at least one eligible surgical hip and knee surgery discharge. The total number of such discharges was 26,144. On average, there were 244.34 CMS-defined hip/knee surgery discharges per hospital. The majority of discharged patients were from urban hospitals (83.37%) in the Southern US (73.07%), without teaching status (87.98%) and with a licensed bed size of 300–499 beds (31.90%). VTE occurred in an average (± standard deviation) of 4.25 ± 6.05 hip/knee surgery discharges per hospital; DVT and PE occurred in 2.44 ± 5.11 and 1.81 ± 1.89 discharges per hospital, respectively. The average length of hospital stay was 7.56 ± 2.88 days in hip/knee discharges with VTE, compared to 4.08 ± 0.59 days in discharges without VTE. Anticoagulation was ordered in 94.70% of discharged patients with DVT and in 89.06% of discharged patients with PE. Under the CMS HAC policy for VTE, the mean loss of revenue per hospital per year was estimated to be 8,453(958,453 (95% confidence interval [CI] 6,902 – 10,005). Per VTE, the average hospital revenue loss was 8,453(952,704 per hospital per year. The mean incremental cost for a hip/knee discharge with VTE, per hospital was 6,581;forDVTandPE,incrementalcostimpactswere6,581; for DVT and PE, incremental cost impacts were 6,581;forDVTandPE,incrementalcostimpactswere6,751 and 8,092,respectively.Theannualcostimpactperhospitalforhip/kneedischargeswithVTEwasestimatedat8,092, respectively. The annual cost impact per hospital for hip/knee discharges with VTE was estimated at 8,092,respectively.Theannualcostimpactperhospitalforhip/kneedischargeswithVTEwasestimatedat31,609 [95% CI 23,714 – 39,505]. Conclusions: The CMS policy on average caused a loss of hospital revenue (≂f$8,500 per year). Additionally, when a VTE event does occur in patients undergoing surgical hip and knee procedures, it is associated with high incremental hospital costs (≂f$32,000). These significant costs will no longer be reimbursed under the new CMS HAC policy. Subsequently, hospitals will be responsible for covering them. Therefore, now more than ever, reducing VTE rates through appropriate prophylaxis of at-risk patients is vital in order for hospitals to lessen the economic impact associated with treating VTE events. The drive to encourage hospitals to provide more efficient and effective healthcare is becoming particularly relevant now that models of health care reform, such as the “Accountable Care Organization”, are being piloted as part of the Senate's Healthcare Reform Bill. This study was funded by sanofi-aventis U.S., Inc. The authors received editorial/writing support in the preparation of this abstract provided by Katherine Roberts, PhD of Excerpta Medica, funded by sanofi-aventis U.S., Inc. Disclosures: Deitelzweig: sanofi-aventis: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Scios: Honoraria, Research Funding, Speakers Bureau; Pfizer: Speakers Bureau. Thompson:sanofi-aventis US Inc.: Employment. Lin:sanofi-aventis US Inc.: Employment, Research Funding. McMorrow:sanofi-aventis US Inc : Research Funding. Johnson:sanofi-aventis US Inc: Research Funding.

Journal of the American College of Cardiology, Mar 1, 2012

Background: This study compares the total medical costs with the use of the new oral anticoagulan... more Background: This study compares the total medical costs with the use of the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban vs. warfarin in the US, based on the results of the ARISTOTLE, RELY and ROCKET-AF trials. Methods: A cost comparison analysis was conducted from the US perspective. The rates of efficacy and safety endpoints for warfarin were estimated as the weighted averages from the ARISTOTLE, RELY and ROCKET-AF trials. The rates of clinical events for NOACs were calculated using the hazard ratios from the original trials. Annual incremental costs associated with clinical events from the US payer perspective were obtained from published literature and inflation adjusted to 2010 cost. Total medical cost avoidance was evaluated for each NOAC vs. warfarin. Results: Based on data from ARISTOTLE, RELY and ROCKET-AF, the per patient year event rates for warfarin treatment were estimated to be 1.24% for ischemic or uncertain type of stroke (IS), 0.75% for myocardial infarction (MI), and 2.83% for major bleeding excluding hemorrhagic stroke (MB). The estimated event rates were IS: 1.14% [

PharmacoEconomics, Dec 21, 2018

Background Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in... more Background Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in nonsurgical patients with acute medical illness. Betrixaban is the first anticoagulant approved in the United States (US) for VTE prophylaxis extending beyond hospitalization. Objective The aim was to establish whether betrixaban for VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the US is cost-effective compared with enoxaparin. Methods A cost-effectiveness analysis was conducted, estimating the cost per quality-adjusted life-year (QALY) gained with betrixaban (35-42 days) compared with enoxaparin (6-14 days) from a US payer perspective over a lifetime horizon. A decision tree (DT) estimated primary VTE events, thrombotic events, and treatment complications in the first 3 months based on data from the phase III Acute Medically Ill VTE Prevention with Extended Duration Betrixaban study. A Markov model estimated recurrent events and long-term complication risks from published literature. EuroQoL-5 Dimensions utility data and costs inflated to 2017 US dollars (US$) were from published literature. Results were discounted at 3.0% per annum. Deterministic and probabilistic sensitivity analyses explored uncertainty. Results Betrixaban dominated enoxaparin, with savings of US$784 and increased QALYs of 0.017 per patient. In addition, betrixaban dominated enoxaparin across all sensitivity analyses, but was most sensitive to utilities and DT probabilities. Furthermore, probabilistic sensitivity analysis found that betrixaban was more cost-effective than enoxaparin at all willingness-to-pay thresholds. Conclusion Betrixaban can be considered cost-effective for nonsurgical patients with acute medical illness at risk of VTE, requiring longer VTE prophylaxis from hospitalization through post-discharge.

Cleveland Clinic Journal of Medicine, Apr 1, 2008

Journal of the American College of Cardiology, Nov 1, 2022

Current Medical Research and Opinion, Dec 8, 2017

Abstract Objective: To conduct a systematic literature review (SLR) and network meta-analysis (NM... more Abstract Objective: To conduct a systematic literature review (SLR) and network meta-analysis (NMA) of real-world studies comparing major bleeding risk among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin. Methods: Systematic searches were conducted in MEDLINE and Embase for full-text articles published between January 1, 2003 and March 18, 2017. Eligible studies compared at least two of the following in a real-world setting: warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban. A Bayesian NMA was conducted to estimate hazard ratios (HRs) for major bleeding using a random-effects model. Results: Eleven studies were included in the NMA. Nine studies included DOACs vs Warfarin comparisons, and four studies included DOACs vs DOACs comparisons (two studies included both comparisons). Median follow-up duration ranged from 2.6–31.2 months. No evidence was identified for edoxaban. Apixaban was associated with a significantly lower risk of major bleeding compared to other oral anticoagulants (warfarin HR = 0.58; 95% credible interval [CrI] = 0.48–0.69; dabigatran = 0.73; 0.61–0.87; rivaroxaban = 0.55; 0.46–0.66). Dabigatran was associated with a significantly lower risk than warfarin (0.79; 0.71–0.88) and rivaroxaban (0.76; 0.67–0.85), and rivaroxaban was not statistically different from warfarin (1.05; 0.91–1.19). Sensitivity analyses with standard dose and sponsorship showed consistent results. Conclusion: DOACs were associated with lower or similar risk of major bleeding compared with warfarin in NVAF patients. Apixaban was associated with a significantly lower risk of major bleeding than other DOACs. Dabigatran was associated with a significantly lower risk of major bleeding compared to rivaroxaban and warfarin.